New insights into autoantibody profiles from immune privileged sites in the eye: a glaucoma study.

Glaucoma is a chronic neurodegenerative disease and one of the leading causes of blindness. Autoantibody based immune processes are assumed to be involved in its pathogenesis. However, it is still unclear to what extent autoantibody patterns found in the eye (aqueous humor) are congruent to systemic autoantibodies (blood). Consistency would underline the specificity of known serum antibody markers for glaucoma. In this study we used antigen microarrays to analyze autoantibody reactivities in sera and corresponding aqueous humor samples of primary open-angle glaucoma patients (N=37) and non-glaucomatous controls (N=31). Compared to control subjects several divergent immunoreactivities were identified for the glaucoma group in both body fluids. Interestingly, 20% of the tested antigens revealed increased immunoreactivities (e.g., against HSP27, MBP, and α-1-antitrypsin) and 7.5% decreased immunoreactivities (e.g., against GFAP and β-L-crystallin), thus demonstrating a significant alteration of the autoantibody profiles in glaucoma patients. Using an artificial neural network in combination with a unique serum autoantibody pattern on prospective sera we were able to detect glaucoma with a specificity and sensitivity of approximately 93%. The intraindividual comparison revealed a strong correlation of detected immunoreactivities in sera and comparative aqueous humor samples in both study groups. These results emphasize the specificity of immunoreactions found in blood samples of glaucoma patients. Furthermore they indicate the necessity of analyzing not only up-regulated but also down-regulated antibody reactivities, which might be likewise relevant for the understanding of other diseases.